This invention relates to an improved process for making 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof, where the end product is obtained in particularly pure form and at high yields in a one-pot procedure.
It is known according to U.S. Pat. No. 4,407,761 to prepare 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid by reacting an aminocarboxylic acid with a phosphonating reactant and then hydrolyzing the reaction mixture by addition of concentrated hydrochloric acid with heating. Problems result from this reaction whereby it does not remain homogeneous and local solidification occurs. This solidificaiton causes variable yields, which in part results from the exothermic nature of the reaction with development of hot spots. Morever, to make the sodium salt utilizing the prior art processes required isolation of 4-amino-1-hydroxybutylidine-1,1-bisphonic acid and an additional step to convert to the monosodium salt.
The present invention solves there problems by allowing the reaction to remain fluid and homogeneous making commerical manufacturing possible, reducing the number of process steps and providing a large improvement in isolated yield of from about 45-50% to about 85-90%.